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2026-01-06

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In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci strains isolated from patients with infective endocarditis

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https://doi.org/10.1093/jac/dkaf435

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Background: Infective endocarditis (IE) is a severe infection mainly caused by Staphylococcus aureus, Enterococcus faecalis and viridans streptococci. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are major pathogens in prosthetic valves and devices. Exebacase is a first-in-class, antistaphylococcal lysin with rapid bactericidal and antibiofilm activity. Objective: To assess the in vitro activity of exebacase and standard IE antibiotics against S. aureus and CoNS isolates from IE patients in a university hospital (2010-2020). Methods: A total of 211 consecutive strains were analysed: S. aureus [n = 103 (82 MSSA, 21 MRSA)], S. epidermidis [n = 76 (20 MSSE, 56 MRSE)] and other CoNS species (n = 32, Staphylococcus haemolyticus, Staphylococcus lugdunensis, Staphylococcus hominis, Staphylococcus capitis, Staphylococcus schleiferi, Staphylococcus caprae, Staphylococcus pasteuri). Broth microdilution MICs were determined for exebacase and comparators (cloxacillin, ceftaroline, vancomycin, daptomycin, gentamicin, rifampicin). Results: Exebacase inhibited all S. aureus at ≤1 mg/L. Geometric mean (GM) MICs were 0.56 mg/L for MSSA and 0.49 mg/L for MRSA, with MIC50/90 of 0.5/1 mg/L. For S. epidermidis, GM MICs were 3.03 mg/L (MSSE) and 3.40 mg/L (MRSE), with MIC50/90 of 4/16 and 4/8 mg/L, respectively. Other CoNS showed GM MICs ranging from 0.49 mg/L (S. capitis) to 2.59 mg/L (S. lugdunensis), with intermediate values for S. haemolyticus (1.15), S. hominis (1.0) and S. schleiferi (0.79). Exebacase activity was comparable to β-lactams, vancomycin and daptomycin and remained unaffected by resistance. Conclusions: Exebacase activity was independent of methicillin resistance and consistently higher against S. aureus than S. epidermidis. Further research is warranted to explore lysins in combination against staphylococcal infections.

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Medicaments antibacterians, Estafilococs, Endocarditis

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Antibacterial agents, Staphylococcus, Endocarditis

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Articles publicats en revistes (Medicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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CAÑAS, María alexandra, CUERVO REQUENA, Guillermo, GARCÍA GONZÁLEZ, Javier, KRIVAK, Filip, HERNÁNDEZ MENESES, Marta, FALCES SALVADOR, Carles, PERISSINOTTI, Andrés, VIDAL, Bàrbara, TOLOSANA, José m. (josé maría), SANDOVAL, Elena, QUINTANA, Eduard, LLOPIS PÉREZ, Jaime, MORENO CAMACHO, Ma. asunción, SCHUCH, Raymond, GARCÍA DE LA MÀRIA, Cristina, MIRÓ MEDA, José m.. In vitro exebacase (CF-301) activity against methicillin-susceptible or methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci strains isolated from patients with infective endocarditis. _Journal of Antimicrobial Chemotherapy_. 2026. Vol. 81, núm. 1. [consulta: 24 de març de 2026]. ISSN: 0305-7453. [Disponible a: https://hdl.handle.net/2445/228160]

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